PACE: PD-1 Antibody For dMMR/MSI-H Stage III Colorectal Cancer

Sun Yat-sen University

Status and phase: Enrolling; Phase 3

Conditions: Colorectal Carcinoma

Treatments: Drug: capecitabine; Drug: Sintilimab; Drug: Oxaliplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT05236972

B2021-361-01

Details and patient eligibility

About

In this open-label phase III study, patients with local advanced colon cancer (TanyN+ ,M0, dMMR/MSI-H, at least 10cm from the anus verge)will be scheduled to Group A: receive anti-PD-1 antibody alone (8 cycles, 200mg iv drip Q3W) and Group B (4 or 8 cycles of XELOX: oxaliplatin 130mg/m2 day 1, capecitabine 2000mg/m2 days 1-14, repeated every 21 days). The primary endpoint was 3 Disease-free survival; analyses were done based on all patients with post-randomization data.

Enrollment: 323 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female subjects aged ≥18 years
2. ECOG PS 0/1
3. Histologically proven, stage III (i.e., any T, N1 or N2, M0) adenocarcinoma of the colon (as defined by the presence of the inferior pole of the tumour above the peritoneal reflection - that is, at least 10 cm from the anal margin).
4. Fully surgically resected tumour with clear resection margins (i.e., >1 mm)
5. Locally confirmed defective mismatch repair (dMMR) tumour (as defined by the lack of staining on either the pre-operative biopsy samples or resection specimens of at least one of the following proteins: MLH1 (mutL homolog 1), MSH2 (mutS homologue 2), MSH6 (mutS homolog 6), PMS2
6. Absence of metastases as shown by post-operative CT scan
7. Absence of major post-operative complications or other clinical conditions that, in the opinion of the investigator, would contraindicate adjuvant chemotherapy

Exclusion criteria

1. Rectal tumours (as defined by the presence of the inferior pole of the tumour below the peritoneal reflection - that is, <15 cm from the anal margin).

2. Inability to start adjuvant chemotherapy within 12 weeks after surgery

3. Administration of neoadjuvant systemic chemotherapy or radiotherapy before surgical resection of colon cancer

4. Prior organ transplantation, including allogeneic stem-cell transplantation

5. Significant acute or chronic infections including, among others:

   known history of testing positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) positive test for HBV (Hepatitis B) surface antigen or anti-HCV (Hepatitis C) antibody and confirmatory HCV RNA test

6. Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:

7. Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible

8. Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses ≤10 mg/day of prednisone or equivalent

9. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable

10. Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3 NCI-CTCAE v4.0), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)

11. Persisting toxicity related to prior therapy of Grade >1 NCI-CTCAE v4.0; however, alopecia and sensory neuropathy Grade ≤2 is acceptable unless oxaliplatin administration is planned as part of the adjuvant treatment

12. Pregnancy or lactation

13. Known alcohol or drug abuse

14. Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication

15. Known history of colitis, pneumonitis and pulmonary fibrosis (for example, inflammatory bowel disease, uncontrolled asthma), which, in the opinion of the 16.Investigator, might impair the subject's tolerance of trial treatment.

Any psychiatric condition that would prohibit the understanding or rendering of informed consent 17.Other invasive malignancy within 2 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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323 participants in 2 patient groups

Sintilimab

Experimental group

Description:

Sintilimab 200mg iv drip Q3W for 8 courses

Treatment:

Drug: Sintilimab

XELOX

Experimental group

Description:

Patients receive chemotherapy comprising oxaliplatin 130mg/m² ivdrip over 2 hours on day 1,capecitabine 2000 mg/m² on days 1-14, treatment repeats every 21 days for 4 or 8 courses

Treatment:

Drug: capecitabine

Drug: Oxaliplatin